1887

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Volume 70, Issue 12

Organ Distribution of Proteinase-resistant Prion Protein in Humans and Mice with Creutzfeldt-Jakob Disease Free

Abstract

SUMMARY

We attempted to clarify the organ distribution of human and murine proteinase-resistant prion protein (PrP)in Creutzfeldt-Jakob disease (CJD), and to measure the concentration of PrP, using a semi-quantitative Western blot analysis. Human PrP was restricted to the central nervous system, whereas murine PrP was present in the central nervous system and in the lymphoreticular system at the end stage of CJD. PrP concentration in the central nervous system of mice was almost identical to that of humans. The minimum wet weight of an organ with a positive reaction was 0·3 mg for brain, 1 to 3 mg for spleen, 3 mg for spinal cord, 3 mg for lymph node, 10 mg for thymus and 10 to 30 mg for intestine of the CJD-infected mice. There were no immunoreactions in purified PrP fractions from 300 mg of spleen, lymph node, liver or peripheral nervous systems of humans, nor in 300 mg of liver, lung or kidney of CJD-infected mice. Within the limits of our method, the distribution of murine PrP differed from that of human PrP. Antibodies on the Western blot membrane from murine spleen PrP fractions stained the kuru plaques in the CJD-infected mouse brain. Therefore, PrP in the murine spleen probably shares the epitopes of the antigen in the murine kuru plaques. Although the immunological detection of PrP does have limits of sensitivity, PrP concentrations did correlate with infectivity titres in scrapie-infected or CJD-infected mice.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Creutzfeldt-Jakob disease , organ distribution and prion protein
© Society for General Microbiology 1989
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1989-12-01
2024-04-18
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References

  1. Bendheim P. E., Barry R. A., Dearmond S. J., Stites D. P., Prusiner S. B. 1984; Antibodies to a scrapie prion protein. Nature, London 310:418–421
     [Google Scholar]
  2. Braig H. R., Diringer H. 1985; Scrapie : concept of a virus-induced amyloidosis of the brain. EMBO Journal 4:2309–2312
     [Google Scholar]
  3. Chesebro B., Race R., Wehrly K., Nishio J., Bloom M., Lechner D., Bergstrom S., Robbins K., Mayer L., Keith J. M., Garon C., Haase A. 1985; Identification of scrapie prion protein-specific mRNA in scrapie-infected and uninfected brain. Nature, London 315:331–333
     [Google Scholar]
  4. Cho H. J. 1986; Antibody to scrapie-associated fibril protein identifies a cellular antigen. Journal of General Virology 67:243–253
     [Google Scholar]
  5. Czub M., Braig H. R., Blode H., Diringer H. 1986; The major protein of SAF is absent from spleen and thus not an essential part of the scrapie agent. Archives of Virology 91:383–386
     [Google Scholar]
  6. Doi S., Ito M., Shinagawa M., Sato G., Isomura H., Goto H. 1988; Western blot detection of scrapie-associated fibril protein in tissues outside the central nervous system from preclinical scrapie-infected mice. Journal of General Virology 69:955–960
     [Google Scholar]
  7. Eklund C. M., Kennedy R. C., Hadlow W. J. 1967; Pathogenesis of scrapie virus infection in the mouse. Journal of Infectious Diseases 117:15–22
     [Google Scholar]
  8. Fraser H., Dickinson A. G. 1970; Pathogenesis of scrapie in the mouse : the role of spleen. Nature, London 226:462–463
     [Google Scholar]
  9. Fraser H., Dickinson A. G. 1978; Studies of the lymphoreticular system in the pathogenesis of scrapie : the role of spleen and thymus. Journal of Comparative Pathology 88:563–573
     [Google Scholar]
  10. Gajdusek D. C., Gibbs C. J. Jr, Alpers M. P. 1966; Experimental transmission of a kuru-like syndrome to chimpanzees. Nature, London 209:794–796
     [Google Scholar]
  11. Gibbs C. J. Jr, Gajdusek D. C., Asher D. M., Alpers M. P., Beck E., Daniel P. M., Mattews W. B. 1968; Creutzfeldt-Jakob disease (subacute spongiform encephalopathy): transmission to the chimpanzee. Science 161:388–389
     [Google Scholar]
  12. Hadlow W. J., Eklund C. M., Kennedy R. C., Jackson T. A., Whitford H. W., Boyle C. C. 1974; Course of experimental scrapie virus infection in the goat. Journal of Infectious Diseases 129:559–567
     [Google Scholar]
  13. Hope J., Multhaup G., Reekie L. J. D., Kimberlin R. H., Beyreuther K. 1988; Molecular pathology of scrapie-associated fibril protein (PrP) in mouse brain affected by the ME7 strain of scrapie. European Journal of Biochemistry 172:271–277
     [Google Scholar]
  14. Kimberlin R. H., Walker C. A. 1977; Characteristics of a short incubation model of scrapie in the golden hamster. Journal of General Virology 34:295–304
     [Google Scholar]
  15. Kitamoto T., Tateishi J. 1988; Immunochemical confirmation of Creutzfeldt-Jakob disease with a long clinical course with amyloid plaque core antibodies. American Journal of Pathology 131:435–443
     [Google Scholar]
  16. Kitamoto T., Hikita K., Tashima T., Tateishi J., Sato Y. 1986a; Scrapie-associated fibrils (SAF) purification method yields amyloid proteins from systemic and cerebral amyloidosis. Bioscience Reports 6:459–465
     [Google Scholar]
  17. Kitamoto T., Tateishi J., Tashima T., Takeshita I., Barry R. A., Dearmond S. J., Prusiner S. B. 1986b; Amyloid plaques in Creutzfeldt-Jakob disease stain with prion protein antibodies. Annals of Neurology 20:204–208
     [Google Scholar]
  18. Kitamoto T., Ogomori K., Tateishi J., Prusiner S. B. 1987; Formic acid pretreatment enhances immunostaining of cerebral and systemic amyloids. Laboratory Investigation 57:230–236
     [Google Scholar]
  19. Kitamoto T., Tateishi J., Sawa H., Doh-Ura K. 1989; Positive transmission of Creutzfeldt-Jakob disease verified by murine kuru plaques. Laboratory Investigation 60:507–512
     [Google Scholar]
  20. Kuroda Y., Gibbs C. J. Jr, Amyx H. L., Gajdusek D. C. 1983; Creutzfeldt-Jakob disease in mice: persistent viremia and preferential replication of virus in low-density lymphocytes. Infection and Immunity 41:154–161
     [Google Scholar]
  21. Laemmli U. K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, London 227:680–685
     [Google Scholar]
  22. McKinley M. P., Bolton D. C., Prusiner S. B. 1983; A protease-resistant protein is a structural component of the scrapie prion. Cell 35:57–62
     [Google Scholar]
  23. Masters C. L., Gajdusek D. C., Gibbs C. J. JR 1981; Creutzfeldt-Jakob disease virus isolations from Gerstmann- Sträussler syndrome : with an analysis of the various forms of amyloid plaque deposition in the virus-induced spongiform encephalopathy. Brain 104:559–588
     [Google Scholar]
  24. Mohri S., Tateishi J. 1989; Host genetic control of incubation periods of Creutzfeldt-Jakob disease in mice. Journal of General Virology 70:1391–1400
     [Google Scholar]
  25. Oesch B., Westaway D., Waelchli M., McKinley M. P., Kent S. B. H., Aebersold R., Barry R. A., Tempst P., Teplow D. B., Hood L. E., Prusiner S. B., Weissmann C. 1985; A cellular gene encodes scrapie PrP 27-30 protein. Cell 40:735–746
     [Google Scholar]
  26. Prusiner S. B. 1982; Novel proteinaceous infectious particles cause scrapie. Science 216:136–144
     [Google Scholar]
  27. Prusiner S. B., Mckinley M. P., Bowman K. A., Bolton D. C., Bendheim P. E., Groth D. F., Glenner G. G. 1983; Scrapie prions aggregate to form amyloid-like birefringent rods. Cell 35:349–358
     [Google Scholar]
  28. Race R. E., Caughey B., Graham K., Ernst D., Chesebro B. 1988; Analyses of frequency of infection, specific infectivity, and prion protein biosynthesis in scrapie-infected neuroblastoma cell clones. Journal of Virology 62:2845–2849
     [Google Scholar]
  29. Rubenstein R., Kascsak R. J., Merz P. A., Papini M. C., Carp R. I., Robakis N. K., Wisniewski H. M. 1986; Detection of scrapie-associated fibril (SAF) proteins using anti-SAF antibody in non-purified tissue preparations. Journal of General Virology671–681
     [Google Scholar]
  30. Shinagawa M., Munekata E., Doi S., Takahashi K., Goto H., Sato G. 1986; Immunoreactivity of a synthetic pentadecapeptide corresponding to the N-terminal region of the scrapie prion protein. Journal of General Virology 67:1745–1750
     [Google Scholar]
  31. Talian J. C., Olmsted J. B., Goldman R. D. 1983; A rapid procedure for preparing fluorescein-labelled specific antibody from whole antiserum: its use in analyzing cytoskeletal architecture. Journal of Cell Biology 97:1277–1282
     [Google Scholar]
  32. Tateishi J., Ohta M., Koga M., Sato Y., Kuroiwa V. 1979; Transmission of chronic spongiform encephalopathy with kuru plaques from human to small rodents. Annals of Neurology 5:581–584
     [Google Scholar]
  33. Tateishi J., Nagara H., Hikita K., Sato Y. 1984a; Amyloid plaques in the brains of mice with Creutzfeldt- Jakob disease. Annals of Neurology 15:278–280
     [Google Scholar]
  34. Tateishi J., Sato Y., Nagara H., Boellaard J. W. 1984b; Experimental transmission of human subacute spongiform encephalopathy to small rodents. IV. Positive transmission from a typical case of Gerstmann- Straussler-Scheinker's disease. Acta neuropathologica 64:85–88
     [Google Scholar]
  35. Tateishi J., Mkita K., Kitamoto T., Nagara H. 1987; Experimental Creutzfeldt-Jakob disease: induction of amyloid plaques in rodents. In Prions – Novel Infectious Pathogens Causing Scrapie and Creutzfeldt-Jakob Disease415–426 Prusiner S. B., McKinley M. P. San Diego: Academic Press;
     [Google Scholar]
  36. Towbin H., Staehlin T., Gordon J. 1979; Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings of the National Academy of SciencesU.S.A 76:4350–4354
     [Google Scholar]
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Organ Distribution of Proteinase-resistant Prion Protein in Humans and Mice with Creutzfeldt-Jakob Disease
J. Gen. Virol. 70, 3371 (1989); https://doi.org/10.1099/0022-1317-70-12-3371
/content/journal/jgv/10.1099/0022-1317-70-12-3371
/content/journal/jgv/10.1099/0022-1317-70-12-3371
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